Dihydro-5-octylfuran-2(3H)-one

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species Wistar rats
Source Dobrá Voda, Slovak Republic
Number and Sex of Animals 6 females
Age at First Dose 9-10 weeks; female animals were non-pregnant and nulliparous
Animal Health Health condition of animals was examined by a veterinarian before initiation of the study.
Acclimation The animals were acclimated under the conditions identical to the conditions during the experiment 5 days prior to the start of treatment. The acclimation was according to the standard operation procedure.
Housing Condition The animals were housed in plastic cages suspended on stainless steel racks, 3 animals per cage in a room equipped with central air-conditioning. The average room temperature was maintained within the range of 22.09 ± 0.21 °C, relative humidity within 54.33 ± 2.34 %. The light regimen was set to a 12-hour light /12-hour dark cycle. Sanitation was performed according to the standard operation procedures.
Diet The laboratory food ssniff (Spezialdiäten GmbH, Germany) was offered at recommended doses each day approximately at the same time. The certificate of analysis is included in the raw data.
Water The animals received tap water for human consumption. Supply of drinking was unlimited. The quality of drinking water is periodical analysed and recorded; certificate of analysis is included in the raw data.
Bedding Lignocel S3/4, Lufa - ITL GmbH, Germany
Animals Identification The animals in the cage were marked by a line (I-III) on the tail with a waterproof marker. Each cage was marked with the study code, ID of animals and date of administration of the test item.
Justification for the Choice of Species Normally females are used for testing according to OECD TG 423 because females are typically the more sensitive gender.

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

The test item was administered in a single dose by gavage using a metal stomach tube. Animals were fasted prior to dosing (food but not water were withheld over-night). Following a period of fasting, animals were weighed and the test item administered. After test item administration, food was withheld for further 3-4 hours.

Doses:

2000 mg/kg

No. of animals per sex per dose:

6

Control animals:

no

Preliminary study:

A limit dose of 2000 mg/kg body weight was used as a starting dose. One group of 3 females was dosed. Test item-related mortality was not observed during 24 hours and therefore, in a second step, another 3 females were treated at the same dose.

Key result

Sex:

female

Dose descriptor:

other: Clinical Observation

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality was observed during the study.

Clinical signs:

other: No mortality was observed during the study. During the follow up period, no animals displayed signs of intoxication, change of health, nor any other adverse reaction.

Gross pathology:

The test item gamma-Dodecalactone administered to 6 females at a limit dose of 2000 mg/kg body weight did not caused death. No signs of toxicity were observed during the first 4 hours in females or the 14-day observation period thereafter. A stagnation of body weight in one animal was observed. The body weights of the rest animals increased during the study. During necropsy, no macroscopic findings were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.
Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the test item is according to UN Globally Harmonized System of Classification, Labelling and Packaging of Chemicals classified Category 5/Unclassified with a LD50 cut off value equal to or greater than 5000 mg/kg body weight according to Regulation (EU) Nr. 1272/2008 (CLP), after single oral administration to Wistar rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species Wistar rats
Source Dobrá Voda, Slovak Republic
Number and Sex of Animals 3 females
Age at First Dose 9-10 weeks; female animals were non-pregnant and nulliparous
Animal Health The health condition of animals was examined by a veterinarian before initiation of the study.
Acclimation The animals were acclimated to the condition identical to the conditions during the experiment 5 days prior to the start of treatment. The acclimation was according to the standard operation procedure.
Housing Condition The animals were housed in plastic cages suspended on stainless steel racks, 1-3 animals per cage, in a room equipped with central air-conditioning. The average room temperature was maintained within the range of 22.10 ± 0.21 °C, relative humidity within 54.30 ± 2.33 %. The light regimen was set to a 12-hour light /12-hour dark cycle. The sanitation was performed according to the standard operation procedures.
Diet A laboratory food ssniff (ssniff Spezialdiäten GmbH) was offered in recommended doses each day approximately at the same time. The certificate of analysis is included in the raw data.
Water The animals received tap water for human consumption. Supply of drinking water was unlimited. The quality of drinking water is periodical analysed (including microbiological control) and recorded; certificate of analysis is included in raw data.
Bedding Lignocel S3/4, Lufa - ITL GmbH, Germany
Animals Identification Each animal was marked with an ID number. Each cage was affixed with a cage card containing pertinent animal and study information. The animals in cages were marked by a line (I-III) on the tail with an ink marker.
Justification for the Choice of Species Normally females are used in the test according to OECD TG 402 because mostly females are the more sensitive gender.

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Approximately 24 hours before the test, fur was removed from the dorsal area of the trunk of the test animals by clipping and shaving. A precise amount of the test item was aspirated into an adjustable pipette and applied directly on the shaved skin of the back in a single dose uniformly over an area approximately 10 % of the total body surface area. Test item was held in contact with the skin by using semi-occlusive dressing with non-irritating tape throughout the 24-hours exposure period. At the end of the exposure period, any residuals of the test item were removed by using lukewarm water without altering the existing response or integrity of the epidermis.

Duration of exposure:

Animals were observed individually immediately after the application of the test item and then 0.5, 1, 2, 4 and 6 hours later. Each animal was inspected daily for the next 14 days.
Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. In addition, the treatment site was observed at 24, 48 and 72 hours after removal of test chemical using the Draize criteria in Table 1.

Table 1 Assessment of the skin reaction according to the Draize et al. scale
Erythema and Eschar Formation Grade
no erythema 0
very slight erythema (barely perceptible) 1
well - defined erythema 2
moderate erythema 3
severe erythema (beet red) to slight eschar formation 4
Total possible erythema score = 4

Oedema Formation Grade
no oedema 0
very slight oedema (barely perceptible) 1
well - defined oedema (edges are well-defined by definite raising) 2
moderate oedema (raised approximately 1 mm) 3
severe oedema (raised more than 1 mm and extending beyond area exposure) 4
Total possible oedema score = 4

Doses:

A limit dose of 2000 mg/kg body weight was used as a starting dose. One female was dosed. Test item-related mortality was not observed during 48-hours exposure period. The sighting study was finished; the main test was started with dose of 2000 mg/kg body weight.

No. of animals per sex per dose:

3

Control animals:

no

Preliminary study:

A limit dose of 2000 mg/kg body weight was used as a starting dose. One female was dosed. Test item-related mortality was not observed during 48-hours exposure period.

Key result

Sex:

female

Dose descriptor:

other: Clinical Observations

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

The test item gamma-Dodecalactone applied to 3 females at a limit dose of 2000 mg/kg body weight did not cause death.

Clinical signs:

other: No signs of toxicity were observed at the dosage of 2000 mg/kg body weight during the first 4 hours or 14-day observation period. No dermal changes were observed. During necropsy no macroscopic findings were noticed.

Gross pathology:

No signs of toxicity were observed at the dosage of 2000 mg/kg body weight during the first 4 hours or 14-day observation period. No dermal changes were observed. During necropsy no macroscopic findings were noticed.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on OECD Guideline 402 it can be concluded, that for the test item gamma-Dodecalactone according to the Globally Harmonised System and Category Labelling of Chemicals can be classified in Category 5/Unclassified after single dermal application to Wistar rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw